Betulinic Acid Alleviates Acute Pancreatitis by Promoting SIRT1-PINK1-Mediated Mitophagy in Acinar Cells

IF 4.2 4区 医学 Q2 CHEMISTRY, MEDICINAL
Zhenfei Yu, Ying Li, Peng An, Xiaoling Qian, Yakun Wang, Bo Wang
{"title":"Betulinic Acid Alleviates Acute Pancreatitis by Promoting SIRT1-PINK1-Mediated Mitophagy in Acinar Cells","authors":"Zhenfei Yu,&nbsp;Ying Li,&nbsp;Peng An,&nbsp;Xiaoling Qian,&nbsp;Yakun Wang,&nbsp;Bo Wang","doi":"10.1002/ddr.70140","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Betulinic acid (BA) has the potential to ameliorate acute pancreatitis (AP); however, the mechanisms have not been fully elucidated. This study aimed to identify the effect of BA on mitophagy and its mediated acetylation. Rat pancreatic acinar AR42J cells were treated with cerulein to simulate AP-induced injury, and then inflammation and mitophagy were evaluated after BA treatment. The molecular mechanisms were analyzed using molecular docking, immunoprecipitation, immunoblotting, and cycloheximide chase assay. The roles of BA and SIRT1 in vivo were assessed by HE staining and enzyme-linked immunosorbent assay. The results showed that BA inhibited inflammation and promoted mitophagy in cerulein-induced AR42J cells. BA combined with SIRT1 and reduced SIRT1-mediated acetylation. Knockdown of SIRT1 counteracted the inflammation and mitophagy caused by BA. Moreover, interference with SIRT1 promoted acetylation of PINK1 to degrade PINK1 protein, which knockdown reversed the inhibition of inflammation and the promotion of mitophagy induced by SIRT1. Additionally, BA inhibited pancreatic tissue injury and inflammation levels in the pancreas in AP mice by regulating SIRT1. In conclusion, BA decelerates the progression of AP by promoting mitophagy and inhibiting inflammation in pancreatic acinar cells. Mechanically, BA increased SIRT1 expression, which knockdown degraded PINK1 protein by inducing acetylation of PINK1.</p>\n </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/ddr.70140","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Betulinic acid (BA) has the potential to ameliorate acute pancreatitis (AP); however, the mechanisms have not been fully elucidated. This study aimed to identify the effect of BA on mitophagy and its mediated acetylation. Rat pancreatic acinar AR42J cells were treated with cerulein to simulate AP-induced injury, and then inflammation and mitophagy were evaluated after BA treatment. The molecular mechanisms were analyzed using molecular docking, immunoprecipitation, immunoblotting, and cycloheximide chase assay. The roles of BA and SIRT1 in vivo were assessed by HE staining and enzyme-linked immunosorbent assay. The results showed that BA inhibited inflammation and promoted mitophagy in cerulein-induced AR42J cells. BA combined with SIRT1 and reduced SIRT1-mediated acetylation. Knockdown of SIRT1 counteracted the inflammation and mitophagy caused by BA. Moreover, interference with SIRT1 promoted acetylation of PINK1 to degrade PINK1 protein, which knockdown reversed the inhibition of inflammation and the promotion of mitophagy induced by SIRT1. Additionally, BA inhibited pancreatic tissue injury and inflammation levels in the pancreas in AP mice by regulating SIRT1. In conclusion, BA decelerates the progression of AP by promoting mitophagy and inhibiting inflammation in pancreatic acinar cells. Mechanically, BA increased SIRT1 expression, which knockdown degraded PINK1 protein by inducing acetylation of PINK1.

Abstract Image

Abstract Image

Abstract Image

白桦酸通过促进sirt1 - pink1介导的腺泡细胞有丝分裂缓解急性胰腺炎
白桦酸(BA)具有改善急性胰腺炎(AP)的潜力;然而,其机制尚未完全阐明。本研究旨在确定BA对线粒体自噬及其介导的乙酰化的影响。用丙核蛋白处理大鼠胰腺腺泡AR42J细胞,模拟ap诱导的损伤,然后观察BA处理后的炎症和线粒体自噬情况。采用分子对接、免疫沉淀、免疫印迹、环己亚胺追踪等方法分析其分子机制。通过HE染色和酶联免疫吸附法评估BA和SIRT1在体内的作用。结果表明,BA抑制了cerulein诱导的AR42J细胞的炎症反应,促进了线粒体自噬。BA与SIRT1联合,减少SIRT1介导的乙酰化。SIRT1的下调可抵消BA引起的炎症和线粒体自噬。此外,干扰SIRT1可促进PINK1乙酰化降解PINK1蛋白,从而逆转SIRT1诱导的炎症抑制和促线粒体自噬。此外,BA通过调节SIRT1抑制AP小鼠胰腺组织损伤和炎症水平。综上所述,BA通过促进胰腺腺泡细胞的线粒体自噬和抑制炎症来减缓AP的进展。机械上,BA增加SIRT1的表达,SIRT1通过诱导PINK1乙酰化来敲低降解的PINK1蛋白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信